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Planar polarization in embryonic epidermis orchestrates global asymmetric morphogenesis of hair follicles

Nature Cell Biology volume 10, pages 12571268 (2008) | Download Citation

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Abstract

Mammalian body hairs align along the anterior–posterior (A–P) axis and offer a striking but poorly understood example of global cell polarization, a phenomenon known as planar cell polarity (PCP). We have discovered that during embryogenesis, marked changes in cell shape and cytoskeletal polarization occur as nascent hair follicles become anteriorly angled, morphologically polarized and molecularly compartmentalized along the A–P axis. Hair follicle initiation coincides with asymmetric redistribution of Vangl2, Celsr1 and Fzd6 within the embryonic epidermal basal layer. Moreover, loss-of-function mutations in Vangl2 and Celsr1 show that they have an essential role in hair follicle polarization and orientation, which develop in part through non-autonomous mechanisms. Vangl2 and Celsr1 are both required for their planar localization in vivo, and physically associate in a complex in vitro. Finally, we provide in vitro evidence that homotypic intracellular interactions of Celsr1 are required to recruit Vangl2 and Fzd6 to sites of cell–cell contact.

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Acknowledgements

We thank J. Murdoch, K. Anderson, M. Kelley, R. Rachel, B. Lake and C. Tabin, for mice and embryos; M. Montcouquiol, S. Sokol and M. Takeiechi for antibodies and reagents; L. Polak, N. Stokes and LARC staff for care and breeding of mice; J. Zallen, S. Sokol and A. vandenBerg for helpful discussions; Alison North and Rockefeller's Bioimaging Resource Centre for assistance with image acquisition and analysis; J. Racelis and A. Firland-Schill for experimental assistance; B. Short, V. Horsley and J. Nowak for advice and critical reading of the manuscript. D.D. is a Ruth L. Kirschstein NRSA postdoctoral fellow. This work was supported by a grant from the National Institutes of Health (R01 AR27883). E.F. is an Investigator of the Howard Hughes Medical Institute.

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Affiliations

  1. Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology & Development, The Rockefeller University, New York, NY 10065, USA.

    • Danelle Devenport
    •  & Elaine Fuchs

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Contributions

D.D. designed, performed and analysed the experiments and wrote the manuscript. E.F. supervised the project and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Elaine Fuchs.

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https://doi.org/10.1038/ncb1784

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